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The Role of Heparanase in the Pathogenesis of Acute Pancreatitis: A Potential Therapeutic Target

Acute pancreatitis (AP) is one of the most common diseases in gastroenterology. However, neither the etiology nor the pathophysiology of the disease is fully understood and no specific or effective treatment has been developed. Heparanase is an endoglycosidase that cleaves heparan sulfate (HS) side...

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Autores principales: Khamaysi, Iyad, Singh, Preeti, Nasser, Susan, Awad, Hoda, Chowers, Yehuda, Sabo, Edmond, Hammond, Edward, Gralnek, Ian, Minkov, Irena, Noseda, Alessandro, Ilan, Neta, Vlodavsky, Israel, Abassi, Zaid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429646/
https://www.ncbi.nlm.nih.gov/pubmed/28386074
http://dx.doi.org/10.1038/s41598-017-00715-6
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author Khamaysi, Iyad
Singh, Preeti
Nasser, Susan
Awad, Hoda
Chowers, Yehuda
Sabo, Edmond
Hammond, Edward
Gralnek, Ian
Minkov, Irena
Noseda, Alessandro
Ilan, Neta
Vlodavsky, Israel
Abassi, Zaid
author_facet Khamaysi, Iyad
Singh, Preeti
Nasser, Susan
Awad, Hoda
Chowers, Yehuda
Sabo, Edmond
Hammond, Edward
Gralnek, Ian
Minkov, Irena
Noseda, Alessandro
Ilan, Neta
Vlodavsky, Israel
Abassi, Zaid
author_sort Khamaysi, Iyad
collection PubMed
description Acute pancreatitis (AP) is one of the most common diseases in gastroenterology. However, neither the etiology nor the pathophysiology of the disease is fully understood and no specific or effective treatment has been developed. Heparanase is an endoglycosidase that cleaves heparan sulfate (HS) side chains of HS sulfate proteoglycans into shorter oligosaccharides, activity that is highly implicated in cellular invasion associated with cancer metastasis and inflammation. Given that AP involves a strong inflammatory aspect, we examined whether heparanase plays a role in AP. Here, we provide evidence that pancreatic heparanase expression and activity are significantly increased following cerulein treatment. Moreover, pancreas edema and inflammation, as well as the induction of cytokines and signaling molecules following cerulein treatment were attenuated markedly by heparanase inhibitors, implying that heparanase plays a significant role in AP. Notably, all the above features appear even more pronounced in transgenic mice over expressing heparanase, suggesting that these mice can be utilized as a sensitive model system to reveal the molecular mechanism by which heparanase functions in AP. Heparanase, therefore, emerges as a potential new target in AP, and heparanase inhibitors, now in phase I/II clinical trials in cancer patients, are hoped to prove beneficial also in AP.
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spelling pubmed-54296462017-05-15 The Role of Heparanase in the Pathogenesis of Acute Pancreatitis: A Potential Therapeutic Target Khamaysi, Iyad Singh, Preeti Nasser, Susan Awad, Hoda Chowers, Yehuda Sabo, Edmond Hammond, Edward Gralnek, Ian Minkov, Irena Noseda, Alessandro Ilan, Neta Vlodavsky, Israel Abassi, Zaid Sci Rep Article Acute pancreatitis (AP) is one of the most common diseases in gastroenterology. However, neither the etiology nor the pathophysiology of the disease is fully understood and no specific or effective treatment has been developed. Heparanase is an endoglycosidase that cleaves heparan sulfate (HS) side chains of HS sulfate proteoglycans into shorter oligosaccharides, activity that is highly implicated in cellular invasion associated with cancer metastasis and inflammation. Given that AP involves a strong inflammatory aspect, we examined whether heparanase plays a role in AP. Here, we provide evidence that pancreatic heparanase expression and activity are significantly increased following cerulein treatment. Moreover, pancreas edema and inflammation, as well as the induction of cytokines and signaling molecules following cerulein treatment were attenuated markedly by heparanase inhibitors, implying that heparanase plays a significant role in AP. Notably, all the above features appear even more pronounced in transgenic mice over expressing heparanase, suggesting that these mice can be utilized as a sensitive model system to reveal the molecular mechanism by which heparanase functions in AP. Heparanase, therefore, emerges as a potential new target in AP, and heparanase inhibitors, now in phase I/II clinical trials in cancer patients, are hoped to prove beneficial also in AP. Nature Publishing Group UK 2017-04-06 /pmc/articles/PMC5429646/ /pubmed/28386074 http://dx.doi.org/10.1038/s41598-017-00715-6 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Khamaysi, Iyad
Singh, Preeti
Nasser, Susan
Awad, Hoda
Chowers, Yehuda
Sabo, Edmond
Hammond, Edward
Gralnek, Ian
Minkov, Irena
Noseda, Alessandro
Ilan, Neta
Vlodavsky, Israel
Abassi, Zaid
The Role of Heparanase in the Pathogenesis of Acute Pancreatitis: A Potential Therapeutic Target
title The Role of Heparanase in the Pathogenesis of Acute Pancreatitis: A Potential Therapeutic Target
title_full The Role of Heparanase in the Pathogenesis of Acute Pancreatitis: A Potential Therapeutic Target
title_fullStr The Role of Heparanase in the Pathogenesis of Acute Pancreatitis: A Potential Therapeutic Target
title_full_unstemmed The Role of Heparanase in the Pathogenesis of Acute Pancreatitis: A Potential Therapeutic Target
title_short The Role of Heparanase in the Pathogenesis of Acute Pancreatitis: A Potential Therapeutic Target
title_sort role of heparanase in the pathogenesis of acute pancreatitis: a potential therapeutic target
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429646/
https://www.ncbi.nlm.nih.gov/pubmed/28386074
http://dx.doi.org/10.1038/s41598-017-00715-6
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